Disease relevance of SLC24A1

• CONCLUSIONS: Although variant alleles of the rod and cone NCKX genes were found, none could be definitively associated with a specific retinal disease [1].

High impact information on SLC24A1

• The SLC24 gene family Na(+)/Ca(2+)-K(+) exchangers (NCKX) are bidirectional plasma membrane transporters whose main function is the extrusion of Ca(2+) from the cytosol [2].
• NCKX1 is found in retinal rod photoreceptors, while NCKX2 is found in retinal cone photoreceptors and is also widely expressed in the brain [3].
• The Na(+)/Ca(2+)-K(+) exchanger (NCKX) extrudes Ca(2+) from cells utilizing both the inward Na(+) gradient and the outward K(+) gradient [4].
• The Na(+)/Ca(2+)-K(+) exchanger (NCKX) is a polytopic membrane protein that uses both the inward Na(+) gradient and the outward K(+) gradient to drive Ca(2+) extrusion across the plasma membrane [3].
• Human NCKX3 encodes a protein of 644 amino acids that displayed a high level of sequence identity to the other family members, rod NCKX1 and cone/neuronal NCKX2, in the hydrophobic regions surrounding the "alpha -repeat" sequences thought to form the ion-binding pocket for transport [5].

Biological context of SLC24A1

• The single-strand conformation polymorphism (SSCP) technique and direct sequencing were used to screen the patients' DNA for mutations in SLC24A1 and SLC24A2 [1].
• The Na/Ca-K exchanger (NCKX) is a polytopic membrane protein that plays a critical role in Ca(2+) homeostasis in retinal rod and cone photoreceptors [6].
• The genomic organization of the cone NCKX gene was determined, and it contained 11 exons with a few splice variants [1].
• Twenty-five residues were identified for which mutagenesis reduced NCKX function to <20% of wild-type cone NCKX2 activity, while protein expression and plasma membrane targeting were not affected [7].
• METHODS: DNA was collected from unrelated patients with retinal disease, mainly from North America. A human genomic library was screened with the cone NCKX cDNA, and hybridizing clones were sequenced to determine the genomic organization of the SLC24A2 gene [1].

Anatomical context of SLC24A1

• The NCKX1 isoform is found in rods, while the NCKX2 isoform is found in cones, in retinal ganglion cells, and in various parts of the brain [6].
• The Na(+)/Ca(2+)-K(+) exchanger plays a critical role in Ca(2+) homeostasis in retinal rod (NCKX1) and cone (NCKX2) photoreceptors by extruding Ca(2+) that enters rod and cone cells via the cGMP-gated channels [8].
• Taken together, these data provide strong evidence for the expression of NCKX proteins in the vascular smooth muscle and their novel role in mediating agonist-stimulated [Ca2+]cyt and thereby vascular tone [9].
• The purpose of the present study was to identify the expression and function of NCKX in arteries. mRNA encoding NCKX3 and NCKX4 was demonstrated by RT-PCR and Northern blot in both rat mesenteric and aortic smooth muscle [9].
• Therefore, we cloned an NCKX from the starfish testes and predicted that it codes for a 616 amino acid protein that is a member of the NCKX family [10].

Associations of SLC24A1 with chemical compounds

• The mass of the cross-link product critically depended on the location of the particular cysteine residue used by the cross-linker, and we cannot exclude that NCKX forms a higher oligomer [11].
• 7. From these results, we conclude that KB-R7943 inhibits the adrenaline plus 5-HT induced aggregation of rabbit and human platelets by inhibiting K(+)-dependent Na(+)/Ca(2+) exchange (NCKX) [12].

Enzymatic interactions of SLC24A1

• In this study we have placed a peptide tag at different positions of the NCKX sequence to examine whether the putative signal sequence is indeed cleaved in either NCKX1 or NCKX2 proteins expressed in heterologous systems [13].

Other interactions of SLC24A1

• The two most conserved regions within the NCKX sequence are known as the alpha1 and alpha2 repeats, and are found within the first and second set of transmembrane domains, respectively [14].

Analytical, diagnostic and therapeutic context of SLC24A1

• Co-immunoprecipitation clearly demonstrated both NCKX homooligomerization and interactions between NCKX and CNG [11].
• The sequence of independent rat NCKX1 clones and the analysis of rat eye mRNA by RT-PCR revealed a region of alternative splicing that comprised four exons and encoded a stretch of 113 amino acids near the beginning of the large cytosolic loop [15].
• Analysis of NCKX1 expression in different rat tissues by Northern blot revealed a very high level of expression of a 7-kb transcript in the eye but also lower levels of transcripts of various lengths in other tissues [15].
• Here, we have used fluorescent in situ hybridization and radiation hybrid mapping to localize the human NCKX1 gene to chromosome 15q22 [16].

References